Developing infections as a side effect of juvenile idiopathic arthritis treatment with biological agents is rare — and in most cases, such infections are either mild or moderate in severity, a study found.
The study, “Infectious adverse events in children with Juvenile Idiopathic Arthritis treated with Biological Agents in a real-life setting: data from the JIRcohorte,” was published in the journal Joint Bone Spine.
Over the last 15 years, the development of new medicines has dramatically improved the outcomes of children diagnosed with juvenile idiopathic arthritis (JIA).
In particular, the advent of biological agents — products that are produced from living organisms or contain components of living organisms — have led to a significant improvement in remission among individuals with JIA. They also have lowered the risk of reduced functional capacity.
However, as biological agents tend to block components of the immune system, their use can lead to undesired side effects, such as immunosuppression (partial or complete suppression of the immune system). As such, patients treated with biological agents are thought to be at a higher risk for infections.
Studies of adults treated with such agents have shown an increased risk of infection, particularly severe infections and tuberculosis. In children, however, very little is known about the risk of infections as a long-term effect of biological agents.
Researchers now conducted a study to determine the infectious adverse events occurring in children with JIA who were treated with biological agents, depending on type of treatment and initial diagnosis.
Patients were selected from the JIRcohorte (NCT02377245), an international, multicenter, prospective study composed of children with inflammatory and rheumatological diseases from 15 Pediatric Rheumatologic Centers across four French- speaking countries. Data was collected for the period between January 2001 and August 2015.
All infectious adverse events were retrieved from the database. For every infection, researchers noted the date, severity, need for a hospitalization, type of pathogen, and affected organ.
Incidence rates were relayed in number of events per 100 person-years (100p-y). “Person-years” is a statistic for expressing incidence rates, which takes into account both the number of people in the study and the amount of time each person spends in the study. For example, if 100 people are followed for two years, that is the equivalent of 200 patient-years of follow-up.
The study included 677 patients who were administered biological agents, which comprised a total of 3,075.4 person-years of exposure analyzed. There were 184 infectious events described (6.0 events/100 p-y).
Median age at first use of a biologic was 10.5 years, and median time between diagnosis of JIA and first use of a biologic was 1.5 years. Median time of occurrence of an infectious event since the onset of the treatment was 13.3 months.
Almost all patients (99%) with different types of JIA used Actemra (tocilizumab). People on combination therapy, meaning they were given more than one biologic, represented 90% of the study population.
When broken down by type of biologic agent, there were 15.5 events/100 p-y with Actemra; 9.6 events/100 p-y with Ilaris (canakinumab); 7.4 events/100 p-y with Orencia (abatacept); 6.9/100 p-y with Simponi (golimumab); 6.7/100 p-y with Kineret (anakinra); 6.3/100 p-y with infliximab (trade name Remicade, among other); 4.8/100 p-y with etanercept (trade name Enbrel, Benepali); and 3.7/100 p-y with Humira (adalimumab).
Results indicated that the risk of developing an infection was significantly higher with IL-6 inhibitors, including Actemra, compared with IL-1 inhibitors such as Ilaris, or TNF-inhibitors, which included Remicade, Humira, Simponi or Enbrel.
“The risk of developing a severe or very severe infection was highest with IL-6 inhibitors, followed by IL-1 inhibitors,” the researchers said.
Regarding region of infection, 40.8% of infectious adverse events affected the upper respiratory tract or the ear, nose, and throat (ENT) system.
On severity, 12 infectious adverse events were described as either severe or very severe (0.4/100p-y). Seven of these severe or very severe events occurred in patients with a systemic form of JIA. There were no cases of tuberculosis or death.
“Infectious complications with biologics occurring in children treated for JIA are rare, and in most of the cases have a mild or moderate severity, affecting mainly the upper respiratory tract or the ENT,” the researchers said.